We examined the relationship between whole grain intake and obesity, insulin resistance, inflammation, diabetes and subclinical CVD using baseline data from the Multi-Ethnic Study of Atherosclerosis. Whole grain intake was measured by a 127-item FFQ in 5496 men and women free of CHD and previously known diabetes. Mean whole grain intake was 0·5 (sd 0·5) servings per d; biochemical measures reflect fasting levels. After adjustment for demographic and health behaviour variables, mean differences for the highest quintile of whole grain intake minus the lowest quintile of intake were 0·6 kg/m2 for BMI, 0·36 mg/l for C-reactive protein, 0·82 μmol/l for homocysteine, 0·15 mU/l*mmol/l for homeostasis model assessment (HOMA), 0·48 mU/l for serum insulin, 2·0 mg/dl for glucose and 5·7 % for prevalence of newly diagnosed impaired fasting glucose (glucose ≥ 100 mg/dl or diabetes medication). These differences represent 11–13 % of a standard deviation of BMI, HOMA, glucose and impaired fasting glucose, but 23 %, 52 % and 80 % of a standard deviation of homocysteine, C-reactive protein and insulin, respectively. An inverse association between whole grains and urine albumin excretion was suggested but retained statistical significance after adjustment only in Chinese and Hispanic participants. No associations were observed between whole grain intake and two subclinical disease measures: carotid intima-media thickness and coronary artery calcification. Concordant with previous research, whole grain intake was inversely associated with obesity, insulin resistance, inflammation and elevated fasting glucose or newly diagnosed diabetes. Counter to hypothesis, however, whole grain intake was unrelated to subclinical CVD.